APPLICANT'S ABSTRACT: Cocaine abuse is a major medical concern in the United States, with 2.1 million people estimated to be dependent on cocaine. No pharmacotherapies have been shown to be clinically effective and there is an urgent need for novel therapeutic approaches. This application requests funding for the evaluation of a cocaine vaccine for the treatment of cocaine addiction. The vaccine induces anti-cocaine antibodies which bind to cocaine in the circulation and inhibit its entry into the brain. As a result, the pharmacologic effect of the drug is reduced and it is anticipated that the patient will receive reduced gratification from the use of cocaine. The therapy is intended to help prevent relapse as part of a comprehensive treatment program. The safety and immunogenicity of the cocaine vaccine in humans will be evaluated in a Phase I clinical trial. Subsequent clinical studies will evaluate the safety and efficacy of the vaccine-induced antibody cocaine addiction. The Panel was favorably impressed by all components of the proposal and concluded that the development of a cocaine vaccine is an innovative response to the intent of the SPIRCAP RFA and is strongly supported by preliminary studies in animal models. In addition, the Panel was very favorably impressed by the qualifications of the proposed researchers, especially the program PI and the Project Leader (PL) for Projects 3a and 3b. The Panel found only minor weaknesses in this program. However, they recommended deletion of specific studies in project 2 because of inadequate justification and a reduction in work scope for projects 3b and 4 along with the recommendation to pool the collected data to enhance the efficacy of these two projects. In line with the above recommendation the Panel recommended reduced funding for the Administrative Core and for Projects 2, 3b and 4. The Panel expressed concern about the protection of Human Subjects. The Panel felt strongly that these issues needed to be addressed prior to the initiation of any human subjects trails. DESCRIPTION: This application proposes four years of support for the evaluation of a vaccine to treat cocaine addiction. The vaccine reduces the gratifying affects of cocaine and is designed to help prevent relapse in drug abuse treatment programs. The applicant proposes a project composed of five components that would increase the safety and efficacy of the cocaine vaccine. These components are as follows: Administrative Core -- Barbara S. Fox, Principal Investigator Project 1: Immunogenicity of Cocaine Vaccine in Human Subjects -- Barbara S. Fox, Project Leader Project 2: Evaluation of Cocaine Vaccine in Rat Models of Cocaine Addiction - - Kathleen M. Kantak, Project Leader Project 3a: Active Immunization to Develop Antibodies to Cocaine -- Thomas R. Kosten, Project Leader Project 3b: Immunological Agents for Cocaine Abuse -- Thomas R. Kosten, Project Leader Project 4: Use of a Laboratory Model with Human Research Subjects -- Marian W. Fischman, Project Leader